Lifetime Management of Patients With Severe Aortic Stenosis in the Era of Transcatheter Aortic Valve Replacement.

Aortic stenosis is the most common valvular disease. Surgical aortic valve replacement (SAVR) using mechanical valves has been the preferred treatment for younger patients, but bioprosthetic valves are gaining favour to avoid anticoagulation with warfarin. Transcatheter aortic valve replacement (TAVR) was approved in recent years for the treatment of severe aortic stenosis in intermediate- and low-risk patients as an alternative to SAVR. The longer life expectancy of these groups of patients might exceed the durability of the TAVR or SAVR bioprosthetic valves. Therefore, many patients need 2 or even 3 interventions during their lifetime. Because it has important implications on the feasibility of subsequent procedures, the decision between opting for SAVR or TAVR as the primary procedure requires thorough consideration by the heart team, incorporating patient preferences, clinical indicators, and anatomic aspects. If TAVR is favoured initially, selecting the valve type and determining the implantation level should be conducted, aiming for positive outcomes in the index intervention and keeping in mind the potential for subsequent TAVR-in-TAVR procedures. When SAVR is selected as the primary procedure, the operator must make choices regarding the valve type and the potential need for aortic root enlargement, with the intention of facilitating future valve-in-valve interventions. This narrative review examines the existing evidence concerning the lifelong management of severe aortic stenosis, delving into available treatment strategies, particularly emphasising the initial procedure's selection and its impact on subsequent interventions.

Low-dose coronary calcium scoring CT using a dedicated reconstruction filter for kV-independent calcium measurements.

In this prospective, pilot study, we tested a kV-independent coronary artery calcium scoring CT protocol, using a novel reconstruction kernel (Sa36f). From December 2018 to November 2019, we performed an additional research scan in 61 patients undergoing clinical calcium scanning. For the standard protocol (120 kVp), images were reconstructed with a standard, medium-sharp kernel (Qr36d). For the research protocol (automated kVp selection), images were reconstructed with a novel kernel (Sa36f). Research scans were sequentially performed using a higher (cohort A, n = 31) and a lower (cohort B, n = 30) dose optimizer setting within the automatic system with customizable kV selection. Agatston scores, coronary calcium volumes, and radiation exposure of the standard and research protocol were compared. A phantom study was conducted to determine inter-scan variability. There was excellent correlation for the Agatston score between the two protocols (r = 0.99); however, the standard protocol resulted in slightly higher Agatston scores (29.4 [0-139.0] vs 17.4 [0-158.2], p = 0.028). The median calcium volumes were similar (11.5 [0-109.2] vs 11.2 [0-118.0] mm3; p = 0.176), and the number of calcified lesions was not significantly different (p = 0.092). One patient was reclassified to another risk category. The research protocol could be performed at a lower kV and resulted in a substantially lower radiation exposure, with a median volumetric CT dose index of 4.1 vs 5.2 mGy, respectively (p < 0.001). Our results showed that a consistent coronary calcium scoring can be achieved using a kV-independent protocol that lowers radiation doses compared to the standard protocol. KEY POINTS: • The Sa36f kernel enables kV-independent Agatston scoring without changing the original Agatston weighting threshold. • Agatston scores and calcium volumes of the standard and research protocols showed an excellent correlation. • The research protocol resulted in a significant reduction in radiation exposure with a mean reduction of 22% in DLP and 25% in CTDIvol.

CTA pulmonary artery enlargement in patients with severe aortic stenosis: Prognostic impact after TAVR.

BACKGROUND: Identifying high-risk patients who will not derive substantial survival benefit from TAVR remains challenging. Pulmonary hypertension is a known predictor of poor outcome in patients undergoing TAVR and correlates strongly with pulmonary artery (PA) enlargement on CTA. We sought to evaluate whether PA enlargement, measured on pre-procedural computed tomography angiography (CTA), is associated with 1-year mortality in patients undergoing TAVR. METHODS: We retrospectively included 402 patients undergoing TAVR between July 2012 and March 2016. Clinical parameters, including Society of Thoracic Surgeons (STS) score and right ventricular systolic pressure (RVSP) estimated by transthoracic echocardiography were reviewed. PA dimensions were measured on pre-procedural CTAs. Association between PA enlargement and 1-year mortality was analyzed. Kaplan-Meier and Cox proportional hazards regression analyses were performed. RESULTS: The median follow-up time was 433 (interquartiles 339-797) days. A total of 56/402 (14%) patients died within 1 year after TAVR. Main PA area (area-MPA) was independently associated with 1-year mortality (hazard ratio per standard deviation equal to 2.04 [95%-confidence interval (CI) 1.48-2.76], p â€‹< â€‹0.001). Area under the curve (95%-CI) of the clinical multivariable model including STS-score and RVSP increased slightly from 0.67 (0.59-0.75) to 0.72 (0.72-0.89), p â€‹= â€‹0.346 by adding area-MPA. Although the AUC increased, differences were not significant (p â€‹= â€‹0.346). Kaplan-Meier analysis showed that mortality was significantly higher in patients with a pre-procedural non-indexed area-MPA of ≥7.40 â€‹cm2 compared to patients with a smaller area-MPA (mortality 23% vs. 9%; p â€‹< â€‹0.001). CONCLUSIONS: Enlargement of MPA on pre-procedural CTA is independently associated with 1-year mortality after TAVR.

Ethnic Differences Among Acute Coronary Syndrome Patients in Israel.

AIMS: Life expectancy has increased in Israel during recent decades. However, compared to the majority, mostly Jewish population, life expectancy remains low among Israeli Arabs minority, and cardiovascular diseases are the leading cause of death. We compared baseline characteristics and outcomes between Israeli Arab and non-Arab patients hospitalized with acute coronary syndrome (ACS). METHODS AND RESULTS: A national survey accessed data of 7055 patients (1251, 18% Arabs) hospitalized with ACS. Compared to non-Arab, Arab patients were younger at ACS presentation (59 ± 11 vs. 65 ± 12 years, p < 0.01), more likely male (81% vs. 77%, p = 0.01), and with higher prevalence of diabetes mellitus (47% vs. 34%, p < 0.01) and smoking history (57% vs. 34%, p < 0.001). Among patients with ST-elevation myocardial infarction (STEMI) ACS, the mean time from first medical contact to the hospital was similar for Arab and non-Arab patients (133 and 137 min, respectively). After adjustment for age, gender, time from first medical contact to hospital arrival, diabetes, hypertension and renal failure, 1-year survival was lower among Arab patients (93.4% vs. 95.1%, p = 0.027), and 5-year survival was not statistically different (84.0% vs. 86.8%, p = 0.059). The survival differences were mostly derived from reduced survival at 1 and 5 years of STEMI Arab patients. CONCLUSIONS: Israeli Arabs present with ACS at a younger age than non-Arabs and have higher prevalence of smoking and diabetes at presentation. Adjusted 1-year survival was lower among Arab patients. Access to medical care and in-hospital practices during ACS were similar for Arabs and non-Arabs. The findings highlight the impact of risk factors on the early presentation of ACS and the need for a robust risk reduction program for Israeli Arabs.

Transcatheter Aortic Valve Replacement in Oncology Patients With Severe Aortic Stenosis.

OBJECTIVES: The authors sought to collect data on contemporary practice and outcome of transcatheter aortic valve replacement (TAVR) in oncology patients with severe aortic stenosis (AS). BACKGROUND: Oncology patients with severe AS are often denied valve replacement. TAVR may be an emerging treatment option. METHODS: A worldwide registry was designed to collect data on patients who undergo TAVR while having active malignancy. Data from 222 cancer patients from 18 TAVR centers were compared versus 2,522 "no-cancer" patients from 5 participating centers. Propensity-score matching was performed to further adjust for bias. RESULTS: Cancer patients' age was 78.8 ± 7.5 years, STS score 4.9 ± 3.4%, 62% men. Most frequent cancers were gastrointestinal (22%), prostate (16%), breast (15%), hematologic (15%), and lung (11%). At the time of TAVR, 40% had stage 4 cancer. Periprocedural complications were comparable between the groups. Although 30-day mortality was similar, 1-year mortality was higher in cancer patients (15% vs. 9%; p < 0.001); one-half of the deaths were due to neoplasm. Among patients who survived 1 year after the TAVR, one-third were in remission/cured from cancer. Progressive malignancy (stage III to IV) was a strong mortality predictor (hazard ratio: 2.37; 95% confidence interval: 1.74 to 3.23; p < 0.001), whereas stage I to II cancer was not associated with higher mortality compared with no-cancer patients. CONCLUSIONS: TAVR in cancer patients is associated with similar short-term but worse long-term prognosis compared with patients without cancer. Among this cohort, mortality is largely driven by cancer, and progressive malignancy is a strong mortality predictor. Importantly, 85% of the patients were alive at 1 year, one-third were in remission/cured from cancer. (Outcomes of Transcatheter Aortic Valve Implantation in Oncology Patients With Severe Aortic Stenosis [TOP-AS]; NCT03181997).

Intraprocedural valve-in-valve deployment for treatment of aortic regurgitation following transcatheter aortic valve replacement: An individualized approach.

BACKGROUND: Aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is usually due to paravalvular leak, is more common with self-expanding valves and is associated with adverse outcomes. Treatment of AR with a second valve (valve-in-valve) has been reported, however the mechanism of benefit is unclear. We hypothesized that location of the initial valve in relation to the aortic annulus should guide positioning of the second valve. METHODS: We assessed the outcomes of valve-in-valve deployment for treatment of AR following implantation of self-expanding valves in a single-center TAVR registry. Location of the initial valves was defined as supra-annular, intra-annular or infra-annular according to the position of the device pericardial skirt relative to the annulus. Positioning of the second valve was selected according to the location of the initial valves. RESULTS: Among 285 TAVR patients who received Corevalve or Evolut-R valves, 11 (3.8%) underwent valve-in-valve deployment due to AR. Position of initial valves was supra-annular in 6 cases (group-1), intra-annular in 3 cases (group-2) and infra-annular in 2 cases (group-3). In group-1, second valves were implanted 9 ±â€¯4 mm lower than the initial valves. In group-2, second valves were implanted 7 ±â€¯4 mm higher than the initial valves. In group-3, second valves were implanted 9 ±â€¯1 mm higher than the initial valves. Valve-in-valve deployment reduced AR grade in all 3 groups. CONCLUSIONS: Valve-in-valve deployment decreased AR grade during TAVR procedures. We suggest that positioning of the second valve should be guided by the location of the initial valve relative to the aortic annulus.

Severe Hypertriglyceridemia-Related Pancreatitis: Characteristics and Predictors of Recurrence.

OBJECTIVES: The diagnosis of severe hypertriglyceridemia (HTG) as a cause for acute pancreatitis is often delayed with limited data on the characteristics and predictors of recurrent pancreatitis in this population. METHODS: A regional database of severe HTG level of 1000 mg/dL or greater was analyzed to identify subjects with acute pancreatitis. Factors associated with recurrent pancreatitis during long-term follow-up were investigated. RESULTS: Severe HTG-associated pancreatitis was evident in 171 patients (75% diabetics). Recurrent pancreatitis was observed in 16%; this was associated with younger age, alcohol abuse, and an increase in triglyceride levels. In multivariable analysis, peak triglycerides level of greater than 3000 mg/dL (hazard ratio, 2.92; 95% confidence interval, 1.28-6.64; P = 0.011) and most recent triglycerides level of greater than 500 mg/dL (hazard ratio, 3.72; 95% confidence interval, 1.60-8.66; P = 0.002) remained independently associated with recurrent pancreatitis. These lipid measures as well as alcohol abuse were additionally correlated with a stepwise increase in the number of pancreatitis episodes. CONCLUSIONS: Severe HTG-related pancreatitis was closely associated with diabetes. Extreme HTG and a lack of attainment of lower triglyceride levels were independent long-term predictors of recurrent pancreatitis. These findings emphasize the importance of early identification and successful treatment of severe HTG and its underlying disorders to reduce the burden of recurrent pancreatitis.

Lipoprotein(a) screening in young and middle-aged patients presenting with acute coronary syndrome.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). However, its role in real-world practice and implications for clinical care remains limited. Under investigation herein, are the clinical characteristics associated with increased Lp(a) levels in patients presenting with acute coronary syndrome (ACS). METHODS: Lp(a) was measured at admission in patients ≤ 65 years of age presenting with ACS in a single center. Logistic regression model was used to determine the independent association of clinical characteristics with elevated Lp(a). RESULTS: A total of 134 patients were screened for Lp(a); 83% males, mean age 52 ± 8 years. Median Lp(a) level was 46 nmol/L (interquartile range [IQR] 13-91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented in 32% and associated with younger age at CAD diagnosis. In a multiple logistic regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.48-10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17-5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR 3.18, 95% CI 1.10-9.21, p = 0.033), were independently associated with elevated Lp(a). In contrast, Lp(a) levels were not associated with other traditional cardiovascular risk factors, previous statin treatment, C-reactive protein level or ACS type. CONCLUSIONS: In young and middle-aged patients presenting with ACS, premature CAD, previous revascularization and FH were independently associated with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk. These results, are in accordance with guideline based recommendations for Lp(a) screening, and may be of importance in addressing residual cardiovascular risk in young ACS patients, in light of the novel emerging therapies targeting Lp(a).

Lipid-lowering therapy with PCSK9-inhibitors in the real-world setting: Two-year experience of a regional lipid clinic.

AIM: PCSK9 inhibitors (PCSK9i) effectively lower cholesterol levels in randomized trials with reduction in cardiovascular outcomes and favorable safety profile. However, the access to PCSK9i is limited due to high cost and data regarding the use of PCSK9i in real-world practice is limited. METHODS: Data on all patients submitted for approval of PCSK9i at a regional lipid clinic, outside of clinical trials. Patients' profile, approval rates, low-density lipoprotein cholesterol (LDL-C) reduction rates, and adverse events were evaluated. RESULTS: Recommendation for PCSK9i was given to 133 patients; 16 did not receive insurance approval and additional 16 were approved but did not initiate therapy. Of the 101 treated patients (47% females; mean age 61 ± 11 years), 52 had probable/definite familial hypercholesterolemia (FH) (peak LDL-C level 305 ± 87 mg/dL vs non-FH 204 ± 39 mg/dL) and 62% had an established cardiovascular disease. Statin intolerance was reported by 77%. Follow-up lipid panel was available in 66/101 patients: mean LDL-C reduction was 59% ± 19. Subjects with heterozygous FH had similar LDL-C decrease than those with non-FH (59% ± 22 vs 60% ± 14, P = .792). LDL-C < 100 mg/dL was achieved by 76%, LDL-C < 70 mg/dL by 58% and LDL-C < 40 mg/dL by 18% of those with follow-up data. Side effects were reported by 10%, mainly musculoskeletal complaints and flu-like symptoms, and 15% have discontinued treatment. CONCLUSIONS: Patient selection by a regional lipid clinic resulted in a high real-world PCSK9i insurance approval, with efficacy and safety comparable to randomized clinical trials. Cost and medication nonadherence are potential barriers to successful implementation of therapy in routine clinical care.

Clinical features and outcomes of severe, very severe, and extreme hypertriglyceridemia in a regional health service.

BACKGROUND: Comprehensive data on severe hypertriglyceridemia (HTG) in the general population setting are limited and of importance due to the increase in metabolic risk factors and novel therapies under development. OBJECTIVE: To investigate contributing causes and outcomes of severe to extreme HTG. METHODS: Regional database retrospectively analyzed for subjects with severe HTG. Adverse outcomes were investigated in correlation to HTG severity, with follow-up initiating at first documentation of HTG > 1000 mg/dL. RESULTS: A total of 3091 subjects with severe (peak triglycerides 1000-1999 mg/dL; n = 2590), very severe (2000-2999 mg/dL; n = 369), and extreme (≥3000 mg/dL; n = 132) HTG were identified. Mean age was 48 ± 12 years; 73% males. Obesity (48%) and diabetes (62%) were main contributing factors. During follow-up (median 101 months), 4.7% subjects had pancreatitis, 4.7% myocardial infarction, and 6% stroke. Compared with severe HTG, the multivariate-adjusted hazard ratio for pancreatitis was 3.22 (95% confidence interval 2.21-4.70) for individuals with very severe HTG and 5.55 (3.53-8.71) for those with extreme HTG, P < .0001. In contrast, the extent of HTG severity at these levels was not associated with worse cardiovascular outcomes or death. Most subjects (81%) achieved triglyceride levels <500 mg/dL, associated with lower risk for developing pancreatitis but not myocardial infarction or stroke. CONCLUSIONS: Severity of HTG is closely related to cardiometabolic conditions, with a stepwise increase in the risk for pancreatitis, particularly if not attaining reduced triglyceride levels during the follow-up. In contrast, whereas mild-to-moderate HTG is a known established cardiovascular risk factor, very severe and extreme HTG may not further increase the risk for myocardial infarction, stroke, or mortality.

Increased CD11b+ cells and Interleukin-1 (IL-1) alpha levels during cardiomyopathy induced by chronic adrenergic activation.

BACKGROUND: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure. OBJECTIVES: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation. METHODS: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis. RESULTS: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2. CONCLUSIONS: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

Varying clinical presentations of anomalous origin of the left main coronary artery from the right coronary sinus with an interarterial course in adults.

The diagnosis of anomalous origin of the left main coronary artery from the right coronary sinus with an interarterial course in children and adolescents is considered life-threatening and clinical guidelines recommend surgical correction. The prognostic implications of this diagnosis in adults are not clear. This anomaly may present in adults as sudden cardiac death or may be diagnosed incidentally. Treatment of this anomaly in adults should be tailored individually taking into account the clinical presentation and patient characteristics.

Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). CONCLUSIONS: Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

Outcome of Stent Graft Implantation for Treatment of Access Site Bleeding After Transfemoral Transcatheter Aortic Valve Replacement.

Vascular complications are common after transcatheter aortic valve replacement (TAVR) and are associated with increased morbidity and mortality. Stent graft implantation enables percutaneous treatment of access site bleeding; however, the efficacy and durability and of this approach are unknown. We studied the immediate outcome of stent graft implantation for control of access site bleeding and the need for repeat vascular interventions after stenting, in a cohort of consecutive patients with severe symptomatic aortic stenosis who underwent transfemoral TAVR. Predictors of access site complications requiring percutaneous or surgical vascular repair were identified. Transfemoral TAVR was performed in 194 patients. Access site complications requiring urgent vascular repair occurred in 34 patients (18%). Stent graft implantation was performed in 31 patients and vascular surgery in 3 patients. When patients who required surgical or percutaneous vascular repair were compared with those who did not, increased body mass index (30 ± 6 vs 28 ± 5, p = 0.035) and reduced activated clotting time (233 ± 47 vs 252 ± 47, p = 0.030) were the only predictors of need for vascular repair. Stenting achieved adequate hemostasis in all patients with a single minor vascular complication. During median follow-up of 797 days (interquartile range 585 to 1,173), no clinically significant vascular complications were detected after stenting. In conclusion, control of bleeding was achieved in all patients who underwent stent graft implantation for treatment of access site vascular complications after transfemoral TAVR. None of these patients needed further vascular interventions during follow-up.

Clinical determinants and treatment gaps in familial hypercholesterolemia: Data from a multi-ethnic regional health service.

Background Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community. Methods A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated. Results Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50-74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252-288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p < 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol < 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking. Conclusions The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.